The present invention is directed at an improved method for producing .alpha.-(3,4-disubstituted aryl) cyclic ketones. More specifically, the present invention is directed at a method for preparing (.+-.) - (1R,S)-1-(4-chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone.
A method for producing this compound has been disclosed in European Patent Publication No. 0 230 270, which is directed at fused benzazepines useful in the treatment of psychoses, pain and/or depression. This publication discloses .alpha.-(3,4-disubstituted aryl) cyclic ketones as intermediate XVIII and also discloses a method for producing same. This publication discloses that intermediate XVIII can be prepared by first reacting a 3,4-disubstituted 1-(magnesium halide) phenyl with aryl ketones. The resulting compound is dehydrated using acid catalysts with continuous removal of water. The dehydrated compound then may be converted to a compound of formula XVIII by the sequential use, for example, of m-chloroperbenzoic acid, an alkali metal hydroxide, and then a strong mineral acid. Formula I of the present invention includes the compound of formula XVIII of this publication.
While the process disclosed above produces the desired compounds, the process has the disadvantage of being a multi-step process that proceeds in moderate overall yields.
M. Kosugi, et. al. in J. Chemical Society, Chemical Communications page 344 (1983) and references cited therein disclose a method for .alpha.-phenylation of ketones utilizing a palladium catalyst system and stannyl enolates generated "in situ" from enol acetates and tri-n-butyltin methoxide.
M. A. Cuifolini in J. Organic Chemistry, Volume 53, page 4149 (1988) discloses palladium-catalyzed displacement of halide from aromatic substrates by "soft" enolates (pKa&lt;15). This publication describes the formation of benzo-fused five-or-six-membered rings via intramolecular cyclizations.
I. Kuwajima, et. al. in J. Am. Chem. Soc., Volume 104, page 6831 (1982) disclose a method for palladium catalyzed .alpha.-phenylation of .alpha.-stannyl ketones generated "in situ" from silyl enol ethers and tri-n-butyl tin fluoride. However, each of these three publications utilizes different substrates than those of the presently desired compounds, i.e. the aromatic and ketone portions of the substrates of the subject compounds differ from these publications.
Accordingly, an object of the present invention is a less costly method for producing the compounds of formula I below. ##STR6##